Tratamento da esporotricose felina refratária com a associação de iodeto de potássio e itraconazol oral / Treatment of refractory feline sporotrichosis with the association of potassium iodide and oral itraconazole

A esporotricose é uma micose causada por espécies do complexo Sporothrix. Apesar do itraconazol ser o fármaco de escolha devido a sua efetividade e segurança, casos de falência terapêutica em gatos com esta micose têm sido descritos. O iodeto de potássio em cápsulas é uma opção terapêutica nos casos felinos. Adicionalmente, este fármaco é uma alternativa em pacientes humanos não responsivos ao itraconazol. A associação do iodeto de potássio e agentes antifúngicos pode apresentar melhores resultados quando comparada à monoterapia com estes fármacos. Foi realizado um estudo de coorte, o qual teve como objetivo descrever a resposta terapêutica ao iodeto de potássio em cápsulas via oral (5 mg/kg a cada 24 horas) associado ao itraconazol via oral (100 mg/gato a cada 24 horas) em gatos com esporotricose refratária ao itraconazol, assistidos no Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos do Instituto de Pesquisa Clínica Evandro Chagas/Fiocruz no período de 2012 a 2013. Foram incluídos no estudo 38 gatos, dos quais foi observado cura clínica em 24, falência terapêutica em cinco e óbito em três gatosEm seis casos houve abandono do tratamento. O tempo mediano de tratamento até a cura clínica foi 20 semanas. Vinte e nove animais apresentaram efeitos adversos clínicos, sendo 26 classificados como grau leve. Emagrecimento, hiporexia e vômitos foram os efeitos adversos clínicos mais observados. Quatro animais apresentaram efeitos adversos laboratoriais, representado pelo aumento dos valores das enzimas hepáticas. A utilização de iodeto de potássio em cápsulas associado ao itraconazol se mostrou um esquema terapêutico efetivo e seguro, sendo uma opção na esporotricose felina refratária ao itraconazol.

Sporotrichosis is a fungal infection caused by Sporothrix species complex.Itraconazol is the drug of choice for the treatment of the disease due to itseffectiveness and safety. However, cases of treatment failure in cats have beenreported. Potassium iodide capsules are an option for the feline cases.Additionally, the drug is an alternative to human patients unresponsive toitraconazole. The association of potassium iodide and antifungal agents mayprovide better results when compared to the mono therapy with these drugs. A cohort study was conducted, which aimed to describe the therapeutic response oforal potassium iodide (5 mg/kg every 24 hours) associated with oral itraconazole(100 mg/cat every 24 hours) in cats with sporotrichosis refractory to itraconazole,followed up at the Laboratório de Pesquisa Clínica em Dermatozoonoses emAnimais Domésticos do Instituto de Pesquisa Clínica Evandro Chagas/Fiocruz between 2012 and 2013. Of the 38 cats included in the study, 24 were cured,treatment failure ocurred in five and death in three cats. In six cases there wasnon-compliance with treatment. The median time from treatment until clinical curewith the combination was 20 weeks. Twenty-nine animals presented clinical adverse effects, which were classified as mild in 26 animals. Weight loss,hiporexia and vomiting were the most frequently observed. Four animals showed laboratory adverse effects represented by an increase in liver enzymes. The useof potassium iodide associated with itraconazole has proved to be an effective andsafe therapeutic regimen and, therefore, represents an option in the treatment offeline sporotrichosis refractory to itraconazol.

Success Rate and Risk Factors for Failure of Empirical Antifungal Therapy with Itraconazole in Patients with Hematological Malignancies: A Multicenter, Prospective, Open-Label, Observational Study in Korea

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)

Clinical Outcomes and Prognostic Factors of Empirical Antifungal Therapy with Itraconazole in the Patients with Hematological Malignancies: A Prospective Multicenter Observational Study in Korea

PURPOSE: To identify prognostic factors for the outcomes of empirical antifungal therapy, we performed a multicenter, prospective, observational study in immunocompromised patients with hematological malignancies. MATERIALS AND METHODS: Three hundred seventy-six patients (median age of 48) who had neutropenic fever and who received intravenous (IV) itraconazole as an empirical antifungal therapy for 3 or more days were analyzed. The patients with possible or probable categories of invasive fungal disease (IFD) were enrolled. RESULTS: The overall success rate was 51.3% (196/376). Age >50 years, underlying lung disease (co-morbidity), poor performance status [Eastern Cooperative Oncology Group (ECOG) > or =2], radiologic evidence of IFD, longer duration of baseline neutropenic fever (> or =4 days), no antifungal prophylaxis or prophylactic use of antifungal agents other than itraconazole, and high tumor burden were associated with decreased success rate in univariate analysis. In multivariate analysis, age >50 years (p=0.009) and poor ECOG performance status (p=0.005) were significantly associated with poor outcomes of empirical antifungal therapy. Twenty-two patients (5.9%) discontinued itraconazole therapy due to toxicity. CONCLUSION: We concluded that empirical antifungal therapy with IV itraconazole in immunocompromised patients is effective and safe. Additionally, age over 50 years and poor performance status were poor prognostic factors for the outcomes of empirical antifungal therapy with IV itraconazole.

Resultados de profilaxis con itraconazol 800 mg/día vía oral en adultos con leucemia aguda y neutropenia de alto riesgo: Hospital del Salvador 2006-2008 / Itraconazole 800 mg for the prophylaxis of fungal infections in patients with acute leukemia and severe neutropenia

Background: Systemic fungal infections and specifically invasive aspergillosis (IA) are associated with a high morbi-mortality rate in patients with hematologic malignancies. Itraconazole kinetic studies show that plasma levels are not satisfactory, even though there is a reduction of the severity in clinical cases. Aim: To evaluate the results of oral prophylaxis with high dose itraconazole, 400 mg bid, among patients with adult acute leukemia. Material and Methods: Prospective analysis of 93 high risk febrile episodes (with an absolute neutrophil count of less than 500 x mm3 for more 10 days), that occurred in 76 patients. Results: Seventy five percent of episodes occurred in patients with acute myeloid leukemia and 25 percent in patients with acute lymphoblastic leukemia. Fifty two percent occurred during the induction of chemotherapy. Median duration of severe neutropenia was 21 days (range 10-48). Median duration of itraconazole prophylaxis was 17 days (range 6-34). A low frequency of invasive fungal infections was observed (17 percent). According to diagnostic criteria, 5 percent of episodes corresponded to persistent fever , 1 percent and 11 percent of episodes, to probable or possible IA, respectively. No confirmed or proven IA was observed. Mortality of IA was 18 percent. No serious adverse events due to itraconazole were observed. Conclusions: The use of high dose itraconazole prophylaxis in adult patients with acute leukemia and severe neutropenia was associated to low incidence and mortality of invasive mycoses.

Comparison of the efficacy of clotrimazole and itraconazole in the treatment of acute vulvovaginal candidiasis

A clinical trial to compare the efficacy of clotrimazole and itraconazole in the treatment of vulvovaginal candidiasis. The clinical trial was conducted in the Gynecological outpatient clinic of the University Hospital Amir, Semnan, Iran between the 1st of June 2006 and 31st of June 2007. Vulvovaginal candidiasis was diagnosed by history, examination, smear and culture. Patients [N=264 cases] were divided in two groups. One group was treated with Itraconazole [400mg two divided dose] and the second with clotrimazole vaginal cream [5 grams daily; to be given over 6 days duration]. Patients was considered cured if there were no clinical signs of infection and the smear and culture were negative ten days after the treatment. Statistical analysis for significance was conducted using Student T, chi-square and exact Fisher tests using SPSS package. The mean age of itraconazole and clotrimazole groups were 28.1 +/- 4.8 and 28 +/- 5.8 and cure rates were 88% [110 case] and 81% [103 cases] respectively. There was increased frequency of micturations in 4 cases of itraconazole and 7 cases of clotimazole group and dyspareunia in 2 cases of itraconazole and 6 cases of clotimazole group.The satisfaction rates with treatment were 94.4% [118 cases] and 86% [109 cases] respectively. So, there wasn't any significant statistical difference in cure rate, side effects and satisfaction rate between the two groups. No difference was found in the cure rate for vaginal clotrimazole and oral itraconazole after the treatment of vulvovaginal candidiasis and the side effects of both drugs were minimal

Tratamiento de las micosis profundas. Estado actual / Treatment of deep mycosis. Present state

Se hace una revisión de los antifúngicos disponibles en el mercado internacional en la actualidad, se profundiza más en el anfotericín B, con sus virtudes y reacciones adversas, así como de otros antifúngicos, sobre todo los derivados azoles, imidazólicos y los triazoles, como compuestos con buenos resultados y menos reacciones secundarias, en particular el fluconazol y el itraconazol y sus características

Seguimiento post-terapia en pacientes con paracoccidioidomicosis tratados con itraconazol

De 80 pacientes con paracoccidioidomicosis (PCM) que, a partir de 1985, fueran diagnosticados en los laboratorios de la Corporación para Investigaciones Biológicas (CIB) y que recibieran tratamiento con itraconazol (ITZ), fue posible hacer un seguimiento post-terapia prolongado (promedio de 30 meses, rango 1-8 años) en 53 de ellos. Al momento del diagnóstico, 50 presentaban la forma crónica pulmonar del adulto y los 3 restantes, la forma juvenil. Cuatro de los enfermos estudiados habían recaído después de tratamiento con Ketoconazol. La mayoría de los pacientes (92.4 por ciento) recibieron 100 mgs diarios de ITZ, con una duración promedio de 6 meses de tratamiento en el 62 por ciento de los casos. Ninguno de los pacientes seguidos post-terapia presentó recaída durante el período de observación. Los sítomas más importantes a la terminación de la terapia fueron tos, expertoración y disnea, presentes al final de la terapia en 38.3 por ciento, 22.6 por ciento y 26.4 por ciento de los casos, respectivamente. Su frecuencia, sin embargo, disminuyó durante la observación post-terapia, persistiendo sólo la disnea en 35 por ciento de los casos. El seguimiento radiológico permitió observar la desaparición de los infiltrados retículo-nodulares presentes durante la terapia; sin embargo, la fibrosis fue permanente en 7 de los 11 pacientes que fueron seguidos por más de 4 años. En el 85 por ciento de los pacientes se notó un importante descenso en los títulos de anticuerpos contra el agente causal, P brasiliensis. Los anteriores hallazgos revelan la eficacia del ITZ en el tratamiento de la PCM; se comprueba que este triazol es superior a las drogas para administración oral o intravenosa anteriormente utilizadas ya que no se acompaña de recaídas.

Sporanox en la candidiasis vaginal

Pacientes con candidiasis vagial fueron seleccionadas a participar en un estudio multicéntrico abierto para evaluar el SPORANOX (ITRACONAZOL Janssen) un día de tratamiento(dos cápsulas 100 mgr tomadas en la mañana y en la noche del mismo día) para evaluar el flujo y la sintomatología vulvar y vaginal(eritema, edema, prurito); se realizó test de KOH y cultivo a la admisión, una semana después del tratamiento y a las cuatro semanas. Los resultados indican una mejoría significativa de la sintomatología del flujo en la primera semana de observación y 96.5 por ciento en la última semana. Al final de la observación clínica hecha en 266 pacientes incluían cultivos de control de los cuales 240 fueron negativos, indicando una rata de curación del 92 por ciento. No se detectaron efectos colaterales